Subtype-specific intracellular trafficking of alpha2-adrenergic receptors
Daunt, D.A.; Hurt, C.; Hein, L.; Kallio, J.; Feng, F.; Kobilka, B.K.
Molecular Pharmacology 51(5): 711-720
1997
ISSN/ISBN: 0026-895X PMID: 9145909 Document Number: 475614
The three alpha-2-adrenergic receptor subtypes (alpha-2a, alpha-2b, and alpha-2c) are highly homologous G protein-coupled receptors. These receptors all couple to pertussis toxin-sensitive G proteins and have relatively similar pharmacological properties. To further explore functional differences between these receptors, we used immunocytochemical techniques to compare the ability of the three alpha-2-receptor subtypes to undergo agonist-mediated internalization. The alpha-2a-receptor does not internalize after agonist treatment. In contrast, we observed that the alpha-2b-receptor is able to undergo agonist-induced internalization and seems to follow the same endosomal pathway used by the beta-2-adrenergic receptor. Attempts to examine internalization of the alpha-2c-receptor were complicated by the fact that the majority of the alpha-2c-receptor resides in the endoplasmic reticulum and cis/medial Golgi and there is relatively little cell surface localization. Nevertheless, we were able to detect some internalization of the alpha-2c-receptor after prolonged agonist treatment. However, we observed no significant movement of alpha-2c-receptor from the intracellular pool to the plasma membrane during a 4-hr treatment of cells with cycloheximide, suggesting that these cells are unable to process alpha-2c-receptors in the same way they process the alpha-2a or alpha-2b subtypes.